(a) Field of the Invention
This invention relates to a novel and advantageous process for preparing bis(substituted phenyl)phosphorohalidates. In particular, this invention relates to a process for preparing bis(2,4-dichlorophenyl)phosphorochloridate, which is useful as a phosphorylating reagent. More specifically, the process is useful for preparing bis(2,4-dichlorophenyl)phosphorochloridate compositions that are useful in the synthesis of enol phosphate intermediates that can be used in the manufacture of certain carbapenem antibiotics.
(b) Prior Art
Various processes for preparing bis(substituted phenyl)phosphorohalidates have been disclosed. For example, U.S. Pat. No. 3,965,220 discloses a process in which aromatic alcohols and phosphorus halides are allowed to react in the presence of amine catalysts to form various esters of phosphorus acids, including phosphorochloridate esters. Unlike the process of the present invention, however, the process of the U.S. Pat. No. 3,965,220 involves a two-stage procedure in which monoesters are formed initially at 85.degree.-135.degree. (preferably 105.degree.) and diesters are then formed, after addition of more phenol, at 130.degree.-165.degree. (preferably 150.degree.). Although the claims of the U.S. Pat. No. 3,965,220 give a temperature range of 85.degree.-165.degree. for preparing "a mono or di-ester," the specification discloses methods that describe only the range of 85.degree.-135.degree. for monoesters and 130.degree.-165.degree. for diesters. The process of the present invention, by contrast, provides diesters in a one-stage procedure performed within a single temperature range that can be lower than the 130.degree.-165.degree. range required by the U.S. Pat. No. 3,965,220. Moreover, dialkylaminopyridines are not among the amine catalysts disclosed in the U.S. Pat. No. 3,965,220. In the process of the present invention dialkylaminopyridines have been found to possess surprisingly advantageous chemical and physical properties not suggested by the U.S. Pat. No. 3,965,220. The preferred method of isolation used in the present invention provides another distinction from the U.S. Pat. No. 3,965,220: The isolation by crystallization used in the present invention provides a convenient and economically advantageous method for isolating bis(substituted phenyl)phosphorochloridates, in contrast to the distillation method disclosed in the U.S. Pat. No. 3,965,220.
U.S. Pat. No. 3,772,414 discloses a process similar to that of the U.S. Pat. No. 3,965,220 except that various ureas instead of amines are used as catalysts. In addition to the differences discussed above for the U.S. Pat. No. 3,965,220, the present invention differs from the U.S. Pat. No. 3,772,414 in that ureas are not used as catalysts.
U.S. Pat. No. 3,689,602 discloses a process in which 2,4-dichlorophenol and phosphorus oxychloride are allowed to react in the presence of heteroaromatic amines, such as pyridine, to form tris(2,4-dichlorophenyl)phosphate. The U.S. Pat. No. 3,689,602 does not suggest the use of dialkylaminopyridines. Moreover, the U.S. Pat. No. 3,689,602 does not suggest the preparation of phosphorochloridate diesters but is instead specifically limited to the preparation of phosphotriesters.